Increased RB1 abnormalities in human primary prostate cancer following combined androgen blockade.
BACKGROUND
The RB1 proliferation control pathway is a critical determinant of cell cycle progression. Abnormalities of RB1 are found in a variety of cancers, and the association with human prostate cancer (CaP) was examined here.


METHODS
RNA expression levels of RB1 in CaPs were examined by RT-PCR. RNA integrity was assessed by evaluating expression of an endogenous gene standard.


RESULTS
Abnormally low RB1 mRNA expression was found in 12/33 (36%) of CaPs from patients who had received combined androgen blockade (CAB) treatment. In contrast, 6/48 (13%) untreated CaPs showed abnormally low expression. This difference was statistically significant (P = 0.015). In the samples from untreated patients, a higher frequency of abnormal RB1 was found in specimens with a higher Gleason grade (P = 0.038). In addition, one untreated stage C, grade 9 specimen was found to express RB1 transcripts lacking exon 22, as determined by sequencing of DNA from the truncated transcripts.


CONCLUSIONS
These findings suggest that abnormalities of RB1 may contribute to hormone-withdrawal-related survival of CaP cells.
Mack
P C
PC
Department of Internal Medicine, University of California, Davis Cancer Center, Sacramento 95817, USA.
Chi
S G
SG
Meyers
F J
FJ
Stewart
S L
SL
deVere White
R W
RW
Gumerlock
P H
PH
D000726:Androgen Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000502:physiology; D016161:Genes, Retinoblastoma / Q000235:genetics*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D009919:Orchiectomy; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000737:chemistry / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics; D014407:Tumor Cells, Cultured
D000726:Androgen Antagonists; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D007987:Gonadotropin-Releasing Hormone